Advancing Your Clinical Studies of Human Diseases
Gene therapy refers to the technology of modifying or manipulating gene expression or changing the biological characteristics of living cells to achieve disease treatment. According to the timing of gene change, approaches of gene therapy can be divided into two categories: ex vivo and in vivo.
Ex vivo is to repair the genes of cells in culture, and then import the repaired cells into the human body; while in vivo is to directly supply the materials that can change the genes into the human body through the use of a vector.
Animal models constructed with gene-editing technology are a commonly used in vivo approach, these may be used not only to simulate the physiological and pathological environment of human body, but also to simulate the pathological changes of some diseases, due to its potential for high consistency with the development process of diseases.
At present, gene therapy products are used to treat a variety of diseases, including cancer, genetic disorders, and infectious diseases. However, the risks of gene therapy, such as severe immune response (like cytokine storm), neurotoxicity, and insertion mutation (tumorigenicity) have influenced the effectiveness and safety of gene therapy treatments. To minimize the occurrence of these risks, a lot of preclinical research work is needed to lay the foundation for the treatment before applied to human beings. This includes the in vivo animal model construction, vector selection, treatment strategy determination, and more.
Cyagen can provide customers with animal models related to gene therapy, viral vectors, and comprehensive supporting services for scientific researchers:
In preclinical research, gene therapy experiments at the animal model level can improve the evaluation of the feasibility, effectiveness, safety, and immune response of gene therapy, which can greatly improve the reliability of clinical trials.
Cyagen can provide research models and supplemental services to provide for your gene therapy research needs across the fields of immunity, endocrinology, rare diseases, cardiovascular disease (CVD), neurology, and infectious diseases.
| Research Model Services | Details |
|---|---|
| Cyagen Knockout Catalog Models | Over 16,000 ready-to-use knockout (KO)/conditional knockout (cKO) mouse models |
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Custom Mouse & Rat Models (Genetically Modified) |
● Knockout, Conditional Knockout ● Knockin, Conditional Knockin ● Humanization ● Point Mutation ● Transgenic |
| Drug Screening and Assessment Mouse Models |
● Genetically modified tumor mouse/rat models ● Immunodeficient mice ● Syngeneic model ● Human tumor cell line xenotransplantation (CDX) model ● Mice with reconstituted human immune system ● Immune checkpoint (ICP) humanized mice ● Models for metabolic disease and drug efficacy evaluations |
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Animal Model Phenotype Analysis & Supporting Services |
● Animal Surgical & Disease Model Services ● Phenotype Analysis of Mouse and Rat Models ● Breeding Service ● Cryopreservation Service |
>> For more information about gene editing strategy and model selection, Contact us with your project information, and our experts will be in touch within 48 hours.
A viral vector is a kind of gene vector based on a virus. The specific preparation process is to operate and modify the viral genome, to make it carry foreign genes and related gene elements, which are packaged into virus particles. The viral vector carrying a foreign gene is packaged in virus particles to form the gene delivery system.
Comparison of common viral vectors:
| Virus Type | Advantages | Disadvantages |
|---|---|---|
| Retrovirus, Lentivirus |
● Continuous expression ● High infection efficiency ● Low immune response |
● Random insertion of gene fragment ● Risk of causing cancer |
| Adenovirus |
● No gene fragment insertion ● Large vector capacity |
● Poor expression persistence ● High immune response |
| Adeno-associated Virus (AAV) |
● No gene fragment insertion ● Low immune response |
● Poor expression persistence ● Small vector capacity |
The viral vector packaging services for lentivirus, adenovirus, and adeno-associated virus (AAV) provided by Cyagen ensure the reliability of virus packaging quality in terms of virus titer, purity, and activity. Our virus products are widely used in the construction of various cell models, in vivo injection of living animals, gene therapy, and other research fields.
Case 1: Familial Hypercholesterolemia - Adeno-Associated Virus (AAV)-CRISPR/Cas9-Mediated Gene Therapy
The research groups of Dr. Bin Zhou and the team of Dr. Hefeng Huang co-published an article titled "In Vivo AAV-CRISPR/Cas9-mediated Gene Editing Ameliorates Atherosclerosis in Familial Hypercholesterolemia" in the journal Circulation. In this study, researchers find that adeno-associated virus (AAV) delivers CRISPR/Cas9 to achieve LDLR gene correction that can partially rescue LDLR expression and effectively ameliorate atherosclerosis phenotypes in LDLR mutant mice generated by Cyagen. This finding provides a potential therapeutic method for the treatment of familial hypercholesterolemia.
This study revealed that the use of the CRISPR/Cas9 system to target and correct the pathogenic genes of familial hypercholesterolemia can significantly improve atherosclerosis and other related phenotypes. In the future, the CRISPR/Cas9 system delivered by AAV can be used to correct some somatic gene mutations in hereditary cardiovascular diseases, to improve conditions or even repair disease-causing genes.
Case 2: Gene Therapy for Neurodegenerative Diseases
Martin Ingelsson from Uppsala University in Sweden co-published the results of the first Swedish type mutation (APPswe) study with his colleagues using CRISPR/Cas9 to correct amyloid precursor protein in patient cells and mice for the treatment of early-onset autosomal dominant Alzheimer's disease (AD). They knockout mutated APPswe to reduce the production of Aβ in cells of patients, and simultaneously keep the wild-type alleles intact. Using the same strategy, they also modified the genome of transgenic mice carrying the human APPswe allele, but it is not clear whether it will affect AD pathology. The results show that the early-onset AD cases may benefit from the removal of APPswe.
This has led to the development of effective strategies for gene therapy - CRISPR/Cas9 with a viral vector has been used to change the production of abnormal proteins and thus limit the accumulation of abnormal proteins.
